Fluidic Force Microscopy Demonstrates That Homophilic Adhesion by Candida albicans Als Proteins Is Mediated by...

Area of Science:

• Microbiology
• Biophysics
• Biochemistry

Background:

• * *Candida albicans* is a fungal pathogen that forms drug-resistant biofilms, posing challenges in healthcare settings.
• * Cell adhesion and biofilm development are mediated by cell surface agglutinin-like sequence (Als) proteins.
• * While Als proteins form amyloid-like clusters, the role of amyloid bonds in direct cell-cell adhesion was unclear.

Purpose of the Study:

• * To investigate the forces driving intercellular adhesion mediated by Als5, a specific agglutinin-like sequence protein.
• * To determine if amyloid-like bonds form directly between aggregating *Candida albicans* cells.

Main Methods:

• * Utilized an innovative fluidic force microscopy platform to measure forces involved in Als5-mediated adhesion.
• * Assessed the impact of amyloid-forming Als5 expression levels and an antiamyloid peptide on cell-cell binding.
• * Compared binding between cells expressing amyloid-forming Als5 and those with a nonamyloid variant.

Main Results:

• * Strong cell-cell adhesion requires high surface density of amyloid-forming Als5 and is inhibited by an antiamyloid peptide.
• * Binding is significantly reduced between cells expressing amyloid-forming Als5 and those with a nonamyloid form.
• * Homophilic bonding between Als5 proteins on opposing cells, rather than protein-ligand interactions, drives fungal aggregation.

Conclusions:

• * Amyloid-like β-sheet interactions in Als5 play a dual role: forming adhesin nanoclusters (cis-interactions) and mediating direct cell-cell binding (trans-interactions).
• * This novel mechanism of amyloid-based homophilic adhesion may be widespread in microbial adhesins.
• * Targeting this amyloid-based adhesion could be a promising strategy for combating biofilm-associated infections.